Background

Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.

Objective

To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC.

Design, setting, and participants

Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC.

Outcome measurements and statistical analysis

For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance.

Results and limitations

Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p = 0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6–7.7) and 4.1 mo (95% confidence interval: 1.3–4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p = 0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3–4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups.

Conclusions

Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients.

Patient summary

Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.

中文翻译：

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在GETUG-AFU 15的3期临床试验中，对接受雄激素剥夺疗法或多西他赛治疗的男性进行转移性去势初治前列腺癌的抗癌活性和耐受性超出进展。

背景

根据GETUG-AFU 15，CHATEDED和STAMPEDE的结果，雄激素剥夺疗法（ADT）加上多西他赛是适合患有转移性去势，未经历过前列腺癌（mCNPC）的男性的标准治疗方法。对于使用ADT加多西紫杉醇治疗mCNPC的男性，用于转移性去势抵抗性前列腺癌（mCRPC）的治疗效果尚无可用数据。

客观的

为了研究在先接受mCNPC的化学激素治疗的患者的后续治疗的疗效和耐受性。

设计，设置和参与者

收集来自GETUG-AFU 15期3期试验的回顾性数据，以进行mCRPC的治疗。

成果测量和统计分析

对于mCRPC的前三行挽救治疗，我们调查了无生化进展的生存期，最大前列腺特异性抗原（PSA）下降，总体生存期和耐受性。

结果与局限性

总体而言，有245例患者接受了至少一种mCRPC治疗。对于一线使用的多西他赛，仅接受前期ADT和ADT加多西他赛治疗的25/66（38％）和4/20患者（20％）的PSA下降≥50％（p  = 0.14）。中位无生化无进展生存期分别为6.0 mo（95％置信区间：3.6-7.7）和4.1 mo（95％置信区间：1.3-4.9）。对于在一线或二线使用的多西他赛，分别接受前期ADT和ADT加多西他赛治疗的36/80（45％）和4/29患者（14％）的PSA下降≥50％（p = 0.07）。用比卡鲁胺治疗的PSA下降≥50％的患者分别接受了前期ADT和ADT加多西他赛治疗的12/28（43％）和4/23患者（17％）。在接受ADT加多西他赛治疗的男性中，接受阿比特龙或恩杂鲁胺治疗mCRPC的男性中，有10/19例患者（53％）的PSA下降≥50％。很少发生3–4年级事件。研究的局限性包括该分析的观察设计和回顾性特征，没有标准化的治疗方案，并且某些治疗亚组的患者人数有限。

结论

在前期ADT加多西他赛治疗mCNPC后发展为mCRPC后的多西他赛再治疗仅在少数患者中有效。在这种情况下，有关阿比特龙和恩杂鲁胺支持的可用数据保持了疗效。缺乏针对开发mCRPC的男性的标准化治疗方案，限制了患者之间的可比性。

病人总结

仅在有限的接受过化学激素治疗的转移性去势初治前列腺癌患者中，少数接受去势抵抗的多西他赛才有效。建议在这种情况下使用阿比特龙或恩杂鲁胺抗癌活性。